COVID-19 Update April 26, 2020

This blog post is based on Level C evidence – consensus and expert opinion, and some observational data. Examples of protocols, checklists and algorithms are for educational purposes and require modification for your particular needs as well as approval by your hospital before use in clinical practice.

COVID-19 prognosis and mortality rate to help guide goals of care

Richardson S, Hirsch JS, Narasimhan M, et al. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. Published online April 22, 2020. doi:10.1001/jama.2020.6775.

This large observational study of 5700 patients in a North American healthcare setting found a mortality rate in all comers ranging from 5-64% depending on age. Fourteen percent of these patients were ICU patients, 12% were ventilated. Of those patients who were ventilated there was an 88% mortality rate (76% in those aged 18-65 years, 97% on those >65 years old). This is consistent with previous findings of very high mortality rates in ventilated COVID-19 patients. Mortality of non-ventilated patients ages 18-65 years was 20% and mortality of non-ventilated patients >65 years old was 27%. These data are important to know when counseling patients and families about goals of care.

Time spent with patient may be as important as the type of procedure for aerosolization/airborne transmission of COVID-19 virus

There are 3 mechanisms for the production of aerosols that, if inhaled, can deposit in the distal airways:

Laryngeal activity such as talking and coughing

High velocity gas flow; and

Cyclical opening and closure of terminal airways

In this article they suggest that transmission is associated with time in proximity to COVID-19 patients with respiratory symptoms, rather than the procedures per‐se.

“Sneezing and coughing are effective aerosol generators, but all forms of expiration produce particles across a range of sizes. The 5 μm diameter threshold used to differentiate droplet from airborne is an over‐simplification of multiple complex, poorly understood biological and physical variables. The evidence defining aerosol‐generating procedures comes largely from low‐quality case and cohort studies where the exact mode of transmission is unknown as aerosol production was never quantified. We propose that transmission is associated with time in proximity to SARS‐CoV‐1 patients with respiratory symptoms, rather than the procedures per‐se. There is no proven relation between any aerosol‐generating procedure with airborne viral content with the exception of bronchoscopy and suctioning. The mechanism for SARS‐CoV‐2 transmission is unknown but the evidence suggestive of airborne spread is growing. We speculate that infected patients who cough, have high work of breathing, increased closing capacity and altered respiratory tract lining fluid will be significant producers of pathogenic aerosols. We suggest several ‘aerosol‐generating procedures’ may in fact result in less pathogen aerosolisation than a dyspnoeic and coughing patient. Healthcare workers should appraise the current evidence regarding transmission and apply this to the local infection prevalence. Measures to mitigate airborne transmission should be employed at times of risk. However, the mechanisms and risk factors for transmission are largely unconfirmed. Whilst awaiting robust evidence, a precautionary approach should be considered to assure healthcare worker safety.”

Should a healthcare worker wear an N95 mask when providing care for a coughing, possible or confirmed COVID 19 child, when the child will not wear a surgical mask? (care of Laurie Mazurik)

Yes, if a patient is coughing and is a possible or confirmed COVID 19, and cannot keep a surgical mask on, the provider should wear an N95 mask when providing their care. Coughing generates aerosols. This, is why having a coughing patient wear a surgical mask is so important. This applies to all ages. Given that we are all concerned about PPE conservation, if you have to look after these types of patients, it may be best to simply wear the N95 all shift or as long as possible along with the face shield, changing it only if you feel it is contaminated, wet etc.

Mask decontamination and re-use

N95 masks are designed for one time use and there is no manufactured authorized method for their decontamination. National Institute for Occupational Safety and Health (NIOSH) and CDC do not recommend decontamination of respirators as standard of care; however, they outline that when shortage exists, the option of decontamination should be considered. According to the CDC, ultraviolet germicidal irradiation, vaporous hydrogen peroxide, and moist heat using an autoclave show the most promise as methods for decontamination of N95 masks. These methods do not appear to break down filtration or compromise the respirator; however, many of these methods can only be used for limited times.

They autoclave 400 masks in 1.5 hours and redo the process up to 10 times for each N95 (except molded ones). These can only be autoclaved once but if you use other methods for these it goes up to 10 times. University of Manitoba is working with the National Microbiology Lab tested different modes of sterilization and reuse for N95s, and started the whole process.

Andrew Morris COVID-19 update on epidemiology and medical treatment

Asymptomatic and presymptomatic SARS-VoV-2 infection — how do we know who is infectious?

Scripps Researchhave been collating all of this data, and it appears to be somewhere between 42 and 88% of people who are COVID positive, are asymptomatic. If you look closely, the populations vary widely, and the sample sizes remain quite small, with the 3 largest populations on boats (Diamond Princess + 2 aircraft carriers). This aligns with the very recent (and timely) NEJM article which showed that—in a Long Term Care Facility (LTCF)—56% of residents that tested positive were asymptomatic; 89% would develop symptoms; so probably best to refer to them as “presymptomatic”. (Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility. New England Journal of Medicine. 2020.) In addition, over half of these pre-symptomatic patients were shedding live virus.

Congregant settings should be the most targeted sites in this pandemic

There has been dramatic spread of CoV-2 in LTCF, shelters and other congregant settings in Canada. It is likely under–recognized in the US at present, but it is absolutely a recognized problem in Canada, where it continues to be a problem, especially in LTCFs in Quebec and Ontario. An unsurprising congregant setting is a meat–packing facility in Alberta, which has furnished over 600 cases, especially involving workers originally from the Philippines who are major breadwinners for their families back home. It has resulted in several deaths, and is the largest single outbreak in Canada. Congregant settings should be the most targeted sites in this pandemic.

Coordination of RCTs for COVID drugs and organizing of science is of paramount importance

The (now hundreds of) RCTs on potential COVID drugs should be coordinated and properly conducted. A recent article in Lancet Digital Healthargued for this, and made their point based on the available data:

COVID-19 Home testing for health care workers

FDA-approved home testing kits will soon be available for health care workers through a physician’s order, with results available online. Apparently this testing kit has proven to be as accurate as standard CoV-2 nasopharyngeal swab tests (which are not very accurate), although I can not find the data on this anywhere online. Even though this has been approved by the FDA it remains to be determined if these kits are truly reliable.

Kucharski, A et al. Effectiveness of isolation, testing, contact tracing and physical distancing on reducing transmission of SARS-CoV-2 in different settings. Centre for Mathematical Modelling of Infectious Diseases. April 23, 2020.

This group of mathematical modelers used a model of individual-level transmission stratified by setting (household, work, school, other) based on data from 40,162 people in the UK in this non-peer reviewed paper. They simulated the impact of a few different testing, isolation, tracing and physical distancing scenarios. They estimated the reduction in effective reproduction number for a given level of COVID-19 incidence and the number of contacts that would be newly quarantined each day under different strategies. They estimated that combined testing and tracing strategies would reduce transmission more than mass testing or self-isolation alone (50–65% vs 2–30%). If limits were placed on gatherings outside of home/school/work (e.g. maximum of 4 daily contacts in other settings), then manual contact tracing of acquaintances only could have a similar effect on transmission reduction as detailed contact tracing. Strategies that combined isolation of symptomatic cases and tracing of their contacts reduced the effective reproduction number more than mass testing or self-isolation alone.

It looks like moderate physical distancing (max 4 daily contacts outside home/school/work) measures combined with contact tracing (the details of which should be regionalized) is our best bet going forward.

Dipyridamole for COVID-19? Interesting, but not ready for prime time

Elevated D-dimers in patients with COVID-19 have previously been shown to be a marker of poor prognosis. Dipyridamole has been shown in vitro to suppress CoV-2 replication. In this proof of concept trial of oly 31 patients with COVID-19, dipyridamole was associated with lower D-dimers, increased lymphocyte and platelet recovery and clinical improvement (87.5% cure rate, 12.5% clinical remission). Large RCTs are required before any recommendations for clinical use of this drug can be made.

This observational pilot study of 50 patients (with hypoxia on arrival and suspected of having COVID19 who were treated with NRB and nasal cannula supplemental oxygenation), compared SpO2 at triage and after five minutes of proning and looked at post‐proning failure rates of intubation within the first 24 hours. SpO2 improved from 84% to 94%. One quarter of patients failed to improve or maintain their oxygen saturations and required endotracheal intubation within 24 hours of arrival to the ED. While this observational study looks promising for self proning suspected COVID-19 patient in the short term, the duration of potential benefit is not known. RCTs looking at longer time periods and more patient oriented outcomes are needed before routinely employing self-proning in COVID-19 patients.

IDSA COVID-19 treatment guideline recommendations

Among patients who have been admitted to the hospital with COVID-19, the IDSA guideline panel recommends hydroxychloroquine/chloroquine in the context of a clinical trial. (Knowledge gap)

Among patients who have been admitted to the hospital with COVID-19, the IDSA guideline panel recommends hydroxychloroquine/chloroquine plus azithromycin only in the context of a clinical trial. (Knowledge gap)

Among patients who have been admitted to the hospital with COVID-19, the IDSA guideline panel recommends the combination of lopinavir/ritonavir only in the context of a clinical trial. (Knowledge gap)

Among patients who have been admitted to the hospital with COVID-19 pneumonia, the IDSA guideline panel suggests against the use of corticosteroids. (Conditional recommendation, very low certainty of evidence)

Among patients who have been admitted to the hospital with ARDS due to COVID-19, the IDSA guideline panel recommends the use of corticosteroids in the context of a clinical trial. (Knowledge gap)

Among patients who have been admitted to the hospital with COVID-19, the IDSA guideline panel recommends tocilizumab only in the context of a clinical trial. (Knowledge gap)

Among patients who have been admitted to the hospital with COVID-19, the IDSA guideline panel recommends COVID-19 convalescent plasma in the context of a clinical trial. (Knowledge gap)

Based on expert opinion, the most impactful point in the natural history of COVID-19 occurs when oxygen saturation starts to decline. This decline may occur without the patient experiencing subjective shortness of breath (“silent hypoxia”). Hence the suggestion that patients suspected of COVID-19 who are discharged from the ED with normal oxygen saturations should be instructed to monitor their oxygen saturations at home, and to return to the ED when oxygen saturations are persistently lower than baseline. Patients could be provided with a portable oxygenation saturation monitor or could buy one for about $30. If this is not an option, the Roth Score (see below) could be used to estimate oxygen saturation, although it has been criticized because sensitivity and specificity appeared to be presented incorrectly in the original article, and it has not been validated. MDCalc has removed the Roth Score “as it is no longer recommended.” Evidence for the accuracy of smartphone apps for oxygen saturation is all over the map and should probably not be recommended either.

Evidence-based review of psychological impact of quarantine and how to reduce it

There were 24 articles included in this review, most of which reported negative psychological effects including post-traumatic stress symptoms, confusion, and anger. Stressors included longer quarantine duration, infection fears, frustration, boredom, inadequate supplies, inadequate information, financial loss, and stigma. People who are quarantined are more likely to exhibit symptoms of exhaustion, detachment from others, irritability, difficulty sleeping, and poor concentration. Some healthcare workers may suffer from long term psychological consequences such as post traumatic stress, depressive symptoms or alcohol abuse, especially those quarantined > 10 days.

Kucharski, A et al. Effectiveness of isolation, testing, contact tracing and physical distancing on reducing transmission of SARS-CoV-2 in different settings. Centre for Mathematical Modelling of Infectious Diseases. April 23, 2020.

“I am in the present moment. I believe in myself and in the strength of the human spirit. Our society, country, and the world will overcome this. I am an essential part of the process. Even if things are difficult now, I trust the overall path that my life is taking. I’ll start with what I can do today. I accept the situation I am facing. I am confident in my ability to take necessary precautions. Even if I don’t see them now – there are solutions to my problems. I embrace all of my emotions. I let go of the past. I practice gratitude and forgiveness. I look for examples of kindness around me. My level of motivation is increasing. I feel greater amounts of happiness. I trust my intuition. I am doing my best. I effectively handle stress. I adapt and focus on solutions. I persevere. I act from a place of love, compassion, and peace.”

Dr. Anton Helman is an Emergency Physician at North York General in Toronto. He is an Assistant Professor at the University of Toronto, Division of Emergency Medicine and the Education Innovation Lead at the Schwartz-Reisman Emergency Medicine Instititute. He is the founder, editor-in-chief and host of Emergency Medicine Cases.

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